Our recent studies demonstrated that cerebromicrovascular endothelial cells exposed to hypotonic environment in vitro have a full capacity to normalize their volume and membrane potential but a limited capacity to restore the intracellular pH. The present study represents a continuous effort to elucidate the microvascular cellular properties and mechanisms involved in ensuring homeostatically controlled environment in the brain. The response of viable smooth muscle cells to medium of half normal osmolality was similar to that observed in endothelium. It was manifested by immediate cellular swelling without evidence of changes in the permeability to macromolecules or rapid recovery with complete normalization of cell volume. Both cell types (endothelium and smooth muscle) released the following amino acids: taurine, glutamate, aspartate and threonine, apart from K+ ions during normalization of cellular volume. These results strongly suggest that the cerebrovascular endothelium and muscle cells have a built-in capacity for self-regulation which undoubtedly is important for normal function of blood-brain barrier (BBB).